PEBP1 and 15-LO-1 in Asthma: Biomarker Potential for Diagnosis and Severity Stratification

Background: Ferroptosis, a regulated form of cell death characterized by iron-dependent lipid peroxidation, has been implicated in the pathogenesis of asthma. The ferroptosis markers PEBP1 and 15-LO-1 are increasingly recognized as potential biomarkers for asthma. This study investigates the association of these markers with asthma and its severity to evaluate their diagnostic potential. Methods: This cross-sectional study included 45 asthmatic patients and 45 healthy controls. Serum phosphatidylethanolamine-binding protein 1 (PEBP1) and 15-lipoxygenase-1 (15-LO-1) levels were measured using ELISA. Spirometric parameters (FEV₁, FEV₁/FVC ratio, and PEFR) were recorded. A multivariate regression assessed associations between ferroptosis markers and asthma severity. A generalized linear model (GLM) analyzed the relationship between biomarkers (PEBP1 and 15-LO-1) and lung function parameters. A receiver operating characteristic (ROC) analysis evaluated the discriminative capacity of PEBP1 and 15-LO-1. Results: PEBP1 and 15-LO-1 levels were significantly associated with asthma. The multivariate analysis revealed that low PEBP1 levels were strongly associated with asthma and severe asthma (p < 0.001). While elevated 15-LO-1 levels were associated with asthma (p < 0.001), they did not correlate with severity. The ROC analysis demonstrated excellent discriminative capacity for PEBP1 (AUC 0.962, cutoff 1509.8 pg/mL) and 15-LO-1 (AUC 0.895, cutoff 144.8 pg/mL). Lower PEBP1 and higher 15-LO-1 levels were associated with reduced lung function, and lower FEV₁, FEV₁/FVC, and PEF. Older age and female gender were associated with severe asthma. Conclusions: PEBP1 and 15-LO-1 are promising biomarkers for asthma, with PEBP1 showing strong correlations with asthma severity. These findings highlight the potential role of ferroptosis markers in asthma and underscore the need for further longitudinal studies to explore these markers' clinical utility in personalized asthma management.